Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement

Ljungberg, Johan; Janiec, Mikael; Bergdahl, Ingvar A.; Holmgren, Anders; Hultdin, Johan; Johansson, Bengt; Näslund, Ulf; Siegbahn, Agneta; Fall, Tove; Söderberg, Stefan

doi:10.1161/circulationaha.117.030414

Cited by 25 publications

(17 citation statements)

References 31 publications

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“…These data suggest a nuanced role for IL-17 in arterial wall physiology and atherosclerosis pathophysiology. As already discussed, IL-6 and TGF-␤1 are both elevated in CAVD, but in addition there is an association of IL-17RA concentration in the plasma with worsening disease phenotypes (98). These data taken with the literature on Th17 cells in fibrotic diseases and IL-17 in hypertension and atherosclerosis suggest that they may be involved in CAVD.…”

Section: Cytokines In the T Lymphocyte Maturation Paradigmsupporting

confidence: 63%

Adaptive immune cells in calcific aortic valve disease

Raddatz

Madhur

Merryman

2019

American Journal of Physiology-Heart and Circulatory Physiology

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Calcific aortic valve disease (CAVD) is highly prevalent and has no pharmaceutical treatment. Surgical replacement of the aortic valve has proved effective in advanced disease but is costly, time limited, and in many cases not optimal for elderly patients. This has driven an increasing interest in noninvasive therapies for patients with CAVD. Adaptive immune cell signaling in the aortic valve has shown potential as a target for such a therapy. Up to 15% of cells in the healthy aortic valve are hematopoietic in origin, and these cells, which include macrophages, T lymphocytes, and B lymphocytes, are increased further in calcified specimens. Additionally, cytokine signaling has been shown to play a causative role in aortic valve calcification both in vitro and in vivo. This review summarizes the physiological presence of hematopoietic cells in the valve, innate and adaptive immune cell infiltration in disease states, and the cytokine signaling pathways that play a significant role in CAVD pathophysiology and may prove to be pharmaceutical targets for this disease in the near future.

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Section: Cytokines In the T Lymphocyte Maturation Paradigmsupporting

confidence: 63%

Adaptive immune cells in calcific aortic valve disease

Raddatz

Madhur

Merryman

2019

American Journal of Physiology-Heart and Circulatory Physiology

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“…This would also support our original finding of GAL4's association with incident diabetes. 11 Finally, researchers from Sweden, also using the Olink Proseek CVD III panel, 25 reported that GAL4 was associated with aortic stenosis requiring surgery in two separate cohorts and that GAL4 in the discovery cohort was associated with aortic stenosis in the absence of coronary artery disease. The last finding could, however, not be replicated in the validation cohort.…”

Section: Proteins With a Novel Association With Cardiovascular Outcommentioning

confidence: 99%

Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

et al. 2020

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Aims The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. Methods and results Plasma samples from 1713 individuals from the Swedish population-based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid-binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin-like growth factor-binding protein 2 (IGFB2), cathepsin D (CTSD), galectin-4 (GAL4), and paraoxonase-3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all-cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni-corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval:

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“…We used a proximity extension assay (PEA), the Olink Proseek® Multiplex Cardiovascular I 96x96 kit (http://www.olink.com/), simultaneously measuring the concentration of 92 cardiovascular candidate proteins. The mentioned proteomics approach has previously been applied to investigate the relationship between novel protein biomarkers and cardiovascular pathologies [18][19][20]. In short, the assay is performed in a 96-well microplate with 92 pairs of oligonucleotidelabeled antibodies and four internal controls.…”

Section: Multiplex Proximity Extension Assaymentioning

confidence: 99%

The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease

et al. 2020

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Plasma MMP-12 as a potential cardiovascular risk marker in patients with chronic kidney disease (CKD) using a multiplex proteomics method. • Higher levels of MMP-12 are associated with incident CKD in multivariable models adjusted for age, sex, kidney function, and cardiovascular risk factors. • Additional exploration of the utility of proteomic profiling in the clinical setting of patients with CKD is needed.

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Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement

Abstract: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

Cited by 25 publications

References 31 publications

Adaptive immune cells in calcific aortic valve disease

Adaptive immune cells in calcific aortic valve disease

Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease

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